Modeling of drug release from bioerodible polymer matrices

Models for drug release from bioerodible polymer matrices are proposed in this article. We consider that drug is released continually by diffusion that is influenced by polymer chain degradation, and polymer matrix erosion starts and enhances the drug release at a certain time. The models give excellent reproduction of drug release profiles within the whole release period, and the parameters can be correlated to various factors such as γ-irradiation dose, copolymer composition, and initial drug loading, this correlation indicates that the new models can be used to predict the effects of various factors on drug release profiles based on limited experimental data.     

Mathematical modeling of polymer erosion: consequences for drug delivery

Bioerodible polymers have been extensively used as carriers for drug delivery and as scaffolds for tissue engineering. The ability to model and predict erosion behavior can enable the rational design and optimization of biomaterials for various biomedical applications in vivo. This review examines critically the current approaches in mathematical modeling of the erosion of synthetic polymers. The models are classified broadly based on whether they use phenomenological, probabilistic, or empirical approaches. An analysis of the various physical, chemical, and biological factors affecting polymer erosion and the classes of bioerodible polymers to which these analyses have been applied are discussed. The key features and assumptions associated with each of the models are described, and information is provided on the limitations of the models and the various approaches. The review concludes with several directions for future models of polymer erosion.     

Polymer controlled drug delivery system for growth hormone

The use of biomaterials as vehicles for pharmacological agents, hormones, and growth factors is at times the best treatment for controlled local administration. Our study was designed to evaluate the in vitro biocompatibility and potential clinical use of a new polymer, hydroxyethyl methacrylate-vinyl pirrolidone. Human fibroblasts were incubated in the presence of the polymer and/or growth hormone, and evaluation was made of both the rate of polymer and hormone degradation and the proliferative effect on the fibroblast population. Results indicate that this polymer is biodegradable and lacks toxicity toward these cells. The hormone was slowly released, as suggested by enhanced cell proliferation.     

Research progress of in-situ gelling ophthalmic drug delivery system

 Blindness and vision impairment are the most devastating global health problems resulting in a substantial economic and social burden. Delivery of drug to particular parts of the anterior or posterior segment has been a major challenge due to various protective barriers and elimination mechanisms associated with the unique anatomical and physiological nature of the ocular system. Drug administration to the eye by conventional delivery systems results in poor ocular bioavailability (<5%). The designing of a novel approach for a safe, simple, and effective ocular drug delivery is a major concern and requires innovative strategies to combat the problem. Over the past decades, several novel approaches involving different strategies have been developed to improve the ocular delivery system. Among these, the ophthalmic in-situ gel has attained a great attention over the past few years. This review discussed and summarized the recent and the promising research progress of in-situ gelling in ocular drug delivery system.     

Formulation of Fe3O4/acrylate co-polymer nanocomposites as potential drug carriers

Magnetic nanocomposite particles were synthesized by encapsulating nanosized magnetite with an acrylate-based cationic co-polymer made of MMA, BA, and QMA and modifying with MeOPEGMA using the water replacement method. The composition of the co-polymer formulation was optimized based on zeta-potential measurements and freeze-thaw stability. Electrostatic interaction between negatively charged model drug aspirin and positively charged co-polymer plays the most important role in drug loading and in vitro release studies. Drug release exhibited a biphasic profile with an initial burst release followed by a prolonged slow release, which could be potentially useful for target and controlled drug delivery.     

Drug safety, drug quality, drug analysis

Controlling and minimizing the side effects of drugs are the key issues in assuring the safety of drug therapy. Since side effects are inherent properties of the drug material, these cannot be influenced by drug analysts. At the same time drug analysts play a predominant role in assuring the quality of bulk drug materials and drug formulations and this is also closely related to the safety issue. The three main attributes of drug quality are identity, strength and purity. Of these, in the case of bulk drug materials, purity is of prominent importance: by the identification (structure elucidation) and quantitative determination of the impurities and degradation products, the risk of their contribution to the side effect profile of the drug materials can be avoided or at least controlled/minimized. The development in the field of chromatographic and spectroscopic methods in the last decades has led to changes in the philosophy, structure and requirements in the monographs of drug materials in the principal pharmacopoeias. Although the approaches of the European and US Pharmacopoeias are somewhat different, a common feature is the shift of focal point toward purity tests. In contrast to this, relatively few changes are observable in the field of the assay methods for bulk drug materials: non-selective titrimetric and spectrophotometric methods are still widely used. Since the results of these do not contribute to the safety issue, the omission of these tests and substitution by the "mass balance" concept is recommended. The effectiveness of the tendency of replacing non-selective methods by selective ones (mainly HPLC) is also questionable. The reason for this is that due to the limited precision of the HPLC assay the drug content obtained by the mass balance concept is a much better quality control attribute for bulk drug materials than that obtained by HPLC. It is recommended that classical assay methods (including HPLC) be used in exceptional cases only and the time and energy thus spared be used for more important impurity-related issues that directly contribute to the safety of drug therapy.     

分子排阻色谱法测定头孢克肟聚合物

目的:建立用分子排阻色谱法分析头孢克肟高分子聚合物的方法。方法:采用SephadexG10色谱柱（300 mm×16mm,40～120μm）,流动相A为0.1 mol·L^-1磷酸盐缓冲液（pH 7.0）,流动相B为超纯水,流速1.5 ml·min^-1,检测波长:254nm。结果:头孢克肟在5～80 mg·ml^-1范围内与头孢克肟高分子聚合物的峰面积呈良好的线形关系（r=0.999 3）。头孢克肟在5～400μg·ml^-1的范围内与头孢克肟缔合物的峰面积也呈良好的线性关系（r=0.999 7）。结论:该方法能较好地分离头孢克肟与其聚合物,且精密度、准确度均能满足质量控制的要求。     

药物代谢酶在肿瘤耐药性中的研究进展

肿瘤化学治疗法是目前肿瘤治疗最常用且最有效的方法之一,而在肿瘤化疗过程中出现的耐药现象是导致化疗失败的主要原因。肿瘤耐药的产生机制复杂多样,其中药物代谢酶在肿瘤耐药的发生发展中也极为重要。目前研究显示,有多种药物代谢酶如Ⅰ相代谢中的细胞色素P450酶、环氧合酶等,Ⅱ相代谢中的谷胱甘肽转移酶、葡萄糖醛酸转移酶、葡萄糖神经酰胺合成酶、还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）依赖型醌还原酶等以及一类被称作Ⅲ相反应酶类的药物外排泵,如P-糖蛋白等与肿瘤多药耐药的发生密切相关。本文就近年来有关的药物代谢酶与肿瘤耐药的相关性研究作一综述。     

戒毒人员药物渴求度调查问卷的修订

目的：修订戒毒人员药物渴求问卷,为测定药物渴求程度提供有效的测量工具;方法：通过专题访谈等技术,对原问卷题项进行重新审查与筛选,运用探索性因素分析重构了新问卷的理论模型,运用验证性因素分析验证了模型的合理性。结果：修订后的问卷包含29个项目,5个维度。问卷的内部一致性系数在0．807-0．936之间,总问卷及各因子的分半信度为均在0．8以上。验证性因素分析证实问卷具有良好的结构效度;吸毒行为变量与问卷各维度之间的高度相关证实问卷具有良好的区分效度。结论：修订后戒毒人员药物渴求度问卷结构清晰,信效度良好。     

医院药品库的科学化管理

医院药品库是医院工作的重要组成部分,是医院采购药品、供应药品、合理管理药品、保证药品质量安全有效的部门。加强药品库管理,确保药品质量,是保障患者用药安全的重要环节。如何管理好药品库,笔者仅提出一些看法与同行们进行探讨,希望把药品库管理提高到更高更新的水平,也是为了更好地为患者服务,为社会服务。     

美沙酮维持治疗门诊受治人群HCV感染及影响因素分析

目的：了解西安市美沙酮维持治疗门诊受治人群丙型肝炎病毒（HCV）感染现状及其特点,为制订相应的干预措施提供科学依据。方法：对西安市美沙酮维持治疗门诊（MMT）2007年5月1日至2008年5月31日入组的404名海洛因依赖者进行问卷调查,并采静脉血检测抗-HCV抗体。结果：404名吸毒者中,抗-HCV阳性率为60．6％。静脉注射史中,曾静脉注射吸毒者280人,抗-HCV阳性率为75．4％,高于非静脉吸毒者的27．4％,差异有统计学意义（P〈0．01）。有14人曾共用注射器具,占3．5％（14／404）。共用注射器具的感染率为78．6％。未共用注射器具者的HCV感染率为60．0％。多性伴者HCV感染率明显高于单一性伴或无性伴者．P〈0．01．有统计学意义。结论：西安市海溶因依籁人群HCV感染率高．相关危险行为普谝存在。     

Polymers for colon targeted drug delivery

The colon targeted drug delivery has a number of important implications in the field of pharmacotherapy. Oral colon targeted drug delivery systems have recently gained importance for delivering a variety of therapeutic agents for both local and systemic administration. Targeting of drugs to the colon via oral administration protect the drug from degradation or release in the stomach and small intestine. It also ensures abrupt or controlled release of the drug in the proximal colon. Various drug delivery systems have been designed that deliver the drug quantitatively to the colon and then trigger the release of drug. This review will cover different types of polymers which can be used in formulation of colon targeted drug delivery systems.     

药品合理分类及药品监管制度在医院西药房管理中应用的意义

目的 探讨药品合理分类及药品监管制度在医院西药房管理中的应用价值.方法 以相关规定和药品说明书等为参考,对本院西药房的药品进行合理分类,并且加强药品监管制度.观察比较药品合理分类和加强药品监管制度改进前后各12个月（分别为2011、2012年全年）的药房差错率和患者满意度.结果 2011年1～12月的药房差错率为1.64％,患者满意度为80.31％;2012年1～12月的药房差错率为0.49％,患者满意率为97.83％;两个时间段的药房差错率和患者满意度比较,差异有统计学意义（P＜0.05）.结论 西药房管理中对药品进行分类,加强监督管理,可降低药房差错率,提高患者满意度.     

NMR cryoporometry characterisation studies of the relation between drug release profile and pore structural evolution of polymeric nanoparticles

PLGA/PLA polymeric nanoparticles could potentially enhance the effectiveness of convective delivery of drugs, such as carboplatin, to the brain, by enabling a more sustained dosage over a longer time than otherwise possible. However, the link between the controlled release nanoparticle synthesis route, and the subsequent drug release profile obtained, is not well-understood, which hinders design of synthesis routes and availability of suitable nanoparticles. In particular, despite pore structure evolution often forming a key aspect of past theories of the physical mechanism by which a particular drug release profile is obtained, these theories have not been independently tested and validated against pore structural information. Such validation is required for intelligent synthesis design, and NMR cryoporometry can supply the requisite information. Unlike conventional pore characterisation techniques, NMR cryoporometry permits the investigation of porous particles in the wet state. NMR cryoporometry has thus enabled the detailed study of the evolving, nanoscale structure of nanoparticles during drug release, and thus related pore structure to drug release profile in a way not done previously for nanoparticles. Nanoparticles with different types of carboplatin drug release profiles were compared, including burst release, and various forms of delayed release. ESEM and TEM images of these nanoparticles also provided supporting data showing the rapid initial evolution of some nanoparticles. Different stages, within a complex, varying drug release profile, were found to be associated with particular types of changes in the nanostructure which could be distinguished by NMR. For a core-coat nanoparticle formulation, the development of smaller nanopores, following an extended induction period with no structural change, was associated with the onset of substantial drug release. This information could be used to independently validate the rationale for a particular synthesis method. Hence, the specific reasons for the effectiveness of the synthesis route, for obtaining core-coat nanoparticles with delayed release, have been elucidated.     

Prediction of the drug release stability of different polymeric matrix tablets containing metronidazole

The aim of the present study was to predict the structural changes of polymeric excipients in the course of storage causing undesired changes in drug release stability of tablets containing different polymers. Matrix tablets were formulated with metronidazole as a model drug, using polyvinylpyrrolidone and carbopol as matrix materials. Dissolution tests were carried out before and after storing the tablets under stress conditions for different time intervals. Parameters characterizing the release kinetics of matrix tablets, just as difference and similarity factors, were calculated to compare the release profiles as a function of storage time. FT-IR measurements were carried out to track the structural changes of the physical mixtures of metronidazole and polymers during storage. The changes of the characteristic peaks of the FT-IR spectra of metronidazole-polymer mixtures were in good correlation with the significant changes of release parameters of tablets. The latter was confirmed by ab initio calculations. The work showed that the combination of ab initio calculations with structural examinations could predict the possible instability of drug release and, thus, enables the screening of polymeric excipients of undesired physical stability.     

药物性肝炎及其治疗药物研究

药物在发挥治疗作用的同时,会对肝脏产生毒性或对肝脏致敏导致药物性肝炎。产生药物性肝炎的药物较多,包括中西药制剂,目前尚无明确归类的治疗药物,本文探讨了几种治疗药物;临床上应合理选择药物,结合具体病情,参照保肝药物,以及中医的辨证理论,结合临床实践,确保患者的健康。     

The consequence of the chemical composition of HPMC in matrix tablets on the release behaviour of model drug substances having different solubility

This study investigates the effect of the chemical heterogeneity of hydroxypropyl methylcellulose (HPMC) on the release of model drug substances from hydrophilic matrix tablets. The hypothesis was that the release of drug substances could be influenced by possible interactions with HPMC batches having different chemical heterogeneity. The cloud point of the most heterogeneous batch was more affected by the model drug substances, methylparaben and butylparaben, and most by butylparaben with the lowest solubility. The different clouding behaviour was explained by the heterogeneously substituted batches being more associative and the more lipophilic butylparaben being able to interact more efficiently with the hydrophobic HPMC transient crosslinks that formed. Interestingly, tablet compositions of the heterogeneously substituted HPMC batches released the more soluble methylparaben at lower rates than butylparaben. The explanation is that the hydrophobic HPMC interactions with butylparaben made the gel of the tablet less hydrated and more fragile and therefore more affected by erosional stresses. In contrast, drug release from compositions consisting of the more homogeneously substituted batches was affected to a minor extent by the drugs and was very robust within the experimental variations. The present study thus reveals that there can be variability in drug release depending on the lipophilicity of the drug and the substituent heterogeneity of the HPMC used.     

High-throughput determination of OROS drug release rate profile using micro parallel liquid chromatography

A high throughput method with the use of micro parallel liquid chromatography (μPLC) technique was first applied for the determination of drug release profiles in OROS^® tablets. Currently, high-performance liquid chromatography (HPLC) is a preferred analytical tool to analyze samples released from OROS^® tablets. However, it usually takes more than 20 h to analyze a large number of release rate samples and generate a release-rate profile. In this study, with the use of a 24-column Brio cartridge, the μPLC enabled simultaneous analysis of 24 release-rate samples. The total analysis time including the generation of the release-rate profile was greatly reduced to 3 h. Two different OROS^® formulations were used to compare the drug release testing using both μPLC and conventional HPLC. The drug release profiles generated using μPLC were comparable with those obtained by HPLC. In addition, the reproducibility and sensitivity of μPLC analysis were examined. Overall, significant reductions in analysis time and solvent consumption were the major advantages of using μPLC in profiling the drug release rate for a controlled-release dosage.